There is a growing evidence that Myeloid-derived suppressor cells (MDSCs) have a crucial role in organ transplantation; however, the detail condition where MDSCs are sufficiently induced regarding immunosuppresive function is not clearly understood. We previously described that mTOR inhibition provokes iNOS-expressing MDSCs expansion owing to activation in MEK-ERK signaling pathway. Herein, we present that the ERK signaling pathway is necessary for inducing functional MDSCs in the context of murine cardiac transplantation.

Well-known Aryl hydrocarbon receptor (AhR) agonist: kynurenine (10 mg/kg, intraperitoneally on postoperative days [POD] -7 to 0, 2, 4, and 6) positively recruited Gr-1^int MDSCs and prolonged cardiac graft survival compared with those in the untreated group (11.05 ± 0.75 %, and 5.78 ± 0.53 % on POD 7, 15.5 days vs. 8.0 days, respectively). Splenocytes from kynurenine-treated recipients showed higher ERK phosphorylartion, detected by the cytometric bead array. These effects were sufficiently counterbalanced by the presence of AhR antagonist: CH223191. Furthermore, the administration of an anti-Gr-1, which depleted MDSCs, reduced allograft survival to 9.3 days.

These results demonstrate that MDSCs in the context of cardiac transplantation are regulated by AhR and the ERK signaling pathway. Chronic exposure to AhR agonist might modulate organ transplantation outcomes.

CITATION INFORMATION: Nakamura T, Masuda K, Yoshimura N. Aryl Hydrocarbon Receptor Regulates Myeloid Derived Suppressor Cells by Activating the ERK Signaling in a Murine Cardiac Transplantation Model. Am J Transplant. 2017;17 (suppl 3).

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